Skeletal Muscle Content Research Articles

Differences in intrinsic aerobic capacity alters sensitivity to ischemia-reperfusion injury but not cardioprotective capacity by ischemic preconditioning in rats

IntroductionAerobic capacity is a strong predictor of cardiovascular mortality. Whether aerobic capacity influences myocardial ischemia and reperfusion (IR) injury is unknown.PurposeTo investigate the impact of intrinsic differences in aerobic capacity and the cardioprotective potential on IR injury.MethodsWe studied hearts from rats developed by selective breeding for high (HCR) or low (LCR) capacity for treadmill running. The rats were randomized to: (1) control, (2) local ischemic preconditioning (IPC) or (3) remote ischemic preconditioning (RIC) followed by 30 minutes of ischemia and 120 minutes of reperfusion in an isolated perfused heart model. The primary endpoint was infarct size. Secondary endpoints included uptake of labelled glucose, content of selected mitochondrial proteins in skeletal and cardiac muscle, and activation of AMP-activated kinase (AMPK).ResultsAt baseline, running distance was 203±7 m in LCR vs 1905±51 m in HCR rats (p<0.01). Infarct size was significantly lower in LCR than in HCR controls (49±5% vs 68±5%, p = 0.04). IPC reduced infarct size by 47% in LCR (p<0.01) and by 31% in HCR rats (p = 0.01). RIC did not modulate infarct size (LCR: 52±5, p>0.99; HCR: 69±6%, p>0.99, respectively). Phosphorylaion of AMPK did not differ between LCR and HCR controls. IPC did not modulate cardiac phosphorylation of AMPK. Glucose uptake during reperfusion was similar in LCR and HCR rats. IPC increased glucose uptake during reperfusion in LCR animals (p = 0.02). Mitochondrial protein content in skeletal muscle was lower in LCR than in HCR (0.77±0.10 arbitrary units (AU) vs 1.09±0.07 AU, p = 0.02), but not in cardiac muscle.ConclusionAerobic capacity is associated with altered myocardial sensitivity to IR injury, but the cardioprotective effect of IPC is not. Glucose uptake, AMPK activation immediately prior to ischemia and basal mitochondrial protein content in the heart seem to be of minor importance as underlying mechanisms for the cardioprotective effects.

Antibiotic affects the gut microbiota composition and expression of genes related to lipid metabolism and myofiber types in skeletal muscle of piglets

BackgroundEarly-life antibiotic administration is known to affect gut microbiota and host adiposity, but the effects of antibiotic exposure on skeletal muscle properties remain unknown. The present study evaluated the changes in skeletal muscle properties including myofiber characteristics and composition, as well as intramuscular fat (IMF) content in skeletal muscle of piglets when exposed to a tylosin-containing diet.ResultsA total of 18 piglets (28 days of age) were randomly allocated into two groups: control basal diet (Control) and Control + 100 mg tylosin phosphate/kg of feed (Antibiotic). The trial lasted for 39 days. High-throughput amplicon sequencing revealed that no significant difference in initial gut microbiota composition was existed between Control and Antibiotic groups. Antibiotic administration increased body weight and growth rate and decreased feed to gain ratio of pigs (P < 0.05). The carcass lean and fat volumes of pigs were increased by the tylosin administration (P < 0.05). Antibiotic treatment increased myofiber density and the expression of genes related to type I and type IIb myofibers in longissimus muscle (P < 0.05). The IMF content in longissimus muscle was increased by antibiotic exposure (P < 0.05). Antibiotic administration increased expression of genes related to fatty acid uptake and de novo synthesis, and decreased expression of genes related to triglyceride hydrolysis (P < 0.05). Tylosin administration affected taxonomic distribution and beta diversity of the caecal and colonic microbiota of piglets.ConclusionThese results confirm that the growth performance, myofiber composition and muscle lipid metabolism are affected by antibiotic administration, which may be associated with an altered gut microbiota, suggesting that the gut microbiota could be served as a potential target for modulating skeletal muscle properties of host.

Effects of long-term intradialytic oral nutrition and exercise on muscle protein homeostasis and markers of mitochondrial content in patients on hemodialysis.

Patients with end-stage kidney disease on maintenance hemodialysis commonly develop protein-energy wasting, a syndrome characterized by nutritional and metabolic abnormalities. Nutritional supplementation and exercise are recommended to prevent protein-energy wasting. In a 6-mo prospective randomized, open-label, clinical trial, we reported that the combination of resistance exercise and nutritional supplementation does not have an additive effect on lean body mass measured by dual-energy X-ray absorptiometry. To provide more mechanistic data, we performed a secondary analysis where we hypothesized that the combination of nutritional supplementation and resistance exercise would have additive effects on muscle protein accretion by stable isotope protein kinetic experiments, muscle mass by MRI, and mitochondrial content markers in muscle. We found that 6 mo of nutritional supplementation during hemodialysis increased muscle protein net balance [baseline: 2.5 (-17.8, 13.0) µg·100 mL-1·min-1 vs. 6 mo: 43.7 (13.0, 98.5) µg·100 mL-1·min-1, median (interquartile range), P = 0.04] and mid-thigh fat area [baseline: 162.3 (104.7, 226.6) cm2 vs. 6 mo: 181.9 (126.3, 279.2) cm2, median (interquartile range), P = 0.04]. Three months of nutritional supplementation also increased markers of mitochondrial content in muscle. Although the study is underpowered to detected differences, the combination of nutritional supplementation and exercise failed to show further benefit in protein accretion or muscle cross-sectional area. We conclude that long-term nutritional supplementation increases the skeletal muscle anabolic effect, the fat cross-sectional area of the thigh, and markers of mitochondrial content in skeletal muscle.

Effect of local cold application during exercise on gene expression related to mitochondrial homeostasis

Exercise training increases mitochondrial content in active skeletal muscle. Previous work suggests that mitochondrial-related genes respond favorably to exercise in cold environments. However, the impact of localized tissue cooling is unknown. The purpose of this study was to determine the impact of local muscle cooling during endurance exercise on human skeletal muscle mitochondrial-related gene expression. Twelve subjects (age, 28 ± 6 years) cycled at 65% peak power output. One leg was cooled (C) for 30 min before and during exercise with a thermal wrap while the other leg was wrapped but not cooled, room temperature (RT). Muscle biopsies were taken from each vastus lateralis before and 4 h after exercise for the analysis of gene expression. Muscle temperature was lower in the C (29.2 ± 0.7 °C) than the RT (34.1 ± 0.3 °C) condition after pre-cooling for 30 min before exercise (p < 0.001) and remained lower after exercise in the C (36.9 ± 0.5) than the RT (38.4 ± 0.2, p < 0.001) condition. PGC-1α and NRF1 mRNA expression were lower in the C (p = 0.012 and p = 0.045, respectively) than the RT condition at 4 h after exercise. There were no temperature-related differences in other genes (p > 0.05). These data suggest that local cooling has an inhibitory effect on exercise-induced PGC-1α and NRF1 expression in human skeletal muscle. Those considering using local cooling during exercise should consider other systemic cooling options.Novelty:Local cooling has an inhibitory effect on exercise-induced PGC-1α and NRF1 expression in human skeletal muscle.Local cooling may lead to a less robust exercise stimulus compared with standard conditions.

Response of Mitochondrial Respiration in Adipose Tissue and Muscle to 8 Weeks of Endurance Exercise in Obese Subjects.

Exercise training improves glycemic control and increases mitochondrial content and respiration capacity in skeletal muscle. Rodent studies suggest that training increases mitochondrial respiration in adipose tissue. To assess the effects of endurance training on respiratory capacities of human skeletal muscle and abdominal subcutaneous adipose tissue and to study the correlation with improvement in insulin sensitivity. Using high-resolution respirometry, we analyzed biopsies from 25 sedentary (VO2 peak 25.1 ± 4.0 VO2 mL/[kg*min]) subjects (16 female, 9 male; 29.8 ± 8.4 years) with obesity (body mass index [BMI] 31.5 ± 4.3 kg/m2), who did not have diabetes. They performed a supervised endurance training over 8 weeks (3 × 1 hour/week at 80% VO2 peak). Based on change in insulin sensitivity after intervention (using the Matsuda insulin sensitivity index [ISIMats]), subjects were grouped in subgroups as responders (>15% increase in ISIMats) and low-responders. The response in ISIMats was correlated to a reduction of subcutaneous and visceral adipose tissue volume. Both groups exhibited similar increases in fitness, respiratory capacity, and abundance of mitochondrial enzymes in skeletal muscle fibers. Respiratory capacities in subcutaneous adipose tissue were not altered by the intervention. Compared with muscle fibers, adipose tissue respiration showed a preference for β-oxidation and complex II substrates. Respiratory capacities were higher in adipose tissue from female participants. Our data show that the improvement of peripheral insulin sensitivity after endurance training is not directly related to an increase in mitochondrial respiratory capacities in skeletal muscle and occurs without an increase in the respiratory capacity of subcutaneous adipose tissue.

Goat's Milk Intake Prevents Obesity, Hepatic Steatosis and Insulin Resistance in Mice Fed A High-Fat Diet by Reducing Inflammatory Markers and Increasing Energy Expenditure and Mitochondrial Content in Skeletal Muscle.

Goat’s milk is a rich source of bioactive compounds (peptides, conjugated linoleic acid, short chain fatty acids, monounsaturated and polyunsaturated fatty acids, polyphenols such as phytoestrogens and minerals among others) that exert important health benefits. However, goat’s milk composition depends on the type of food provided to the animal and thus, the abundance of bioactive compounds in milk depends on the dietary sources of the goat feed. The metabolic impact of goat milk rich in bioactive compounds during metabolic challenges such as a high-fat (HF) diet has not been explored. Thus, we evaluated the effect of milk from goats fed a conventional diet, a conventional diet supplemented with 30% Acacia farnesiana (AF) pods or grazing on metabolic alterations in mice fed a HF diet. Interestingly, the incorporation of goat’s milk in the diet decreased body weight and body fat mass, improved glucose tolerance, prevented adipose tissue hypertrophy and hepatic steatosis in mice fed a HF diet. These effects were associated with an increase in energy expenditure, augmented oxidative fibers in skeletal muscle, and reduced inflammatory markers. Consequently, goat’s milk can be considered a non-pharmacologic strategy to improve the metabolic alterations induced by a HF diet. Using the body surface area normalization method gave a conversion equivalent daily human intake dose of 1.4 to 2.8 glasses (250 mL per glass/day) of fresh goat milk for an adult of 60 kg, which can be used as reference for future clinical studies.

Randomized, double blind, placebo controlled clinical study to assess efficacy and safety of NRL/MW/201901 in subjects suffering from erectile dysfunction

Sex is an integral part of a well-being. Sexual satisfaction is the most important component of the quality of life. In management of ED overall sexual potential and quality of life needs to be taken care of as a holistic approach to management. The aim of the study was to clinically validate effect of NRL/MW/201901 a polyhedral Nutraceutical product in ED. The clinical efficacy of NRL/MW/201901 in patients suffering from erectile dysfunction was evaluated by assessing Quality of Erection Questionnaire and sexual encounter profile with Intra-vaginal ejaculation latency time, serum testosterone and anthropometric analysis etc. NRL/MW/201901 was effective in increasing erection function, orgasmic function, intercourse satisfaction, overall satisfaction and sexual desire. There is marked increase in number of sexual encounters in NRL/MW/201901 treated group. Serum levels of testosterone were increased after treatment of NRL/MW/201901 than in placebo group. It was evident from the anthropometric analysis of the subjects that there was significant increase in resting metabolism and % skeletal muscle content in NRL/MW/201901 treated group. There were no evident adverse events related to drug. Thus it could be concluded that NRL/MW/201901 is safe and effective in the treatment of mild to moderate erectile dysfunction.

HIIT Improves Insulin Resistance In T2DM Mice By Regulating Lipid Metabolism In Skeletal Muscle

Abnormal skeletal muscle lipid metabolism is associated with insulin resistance in people with type 2 diabetes. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose and improves insulin resistance in individuals with type 2 diabetes. However, the physical mechanism is largely unknown. PURPOSE: This study aimed to investigate whether HIIT improves insulin resistance in T2DM mice by regulating lipid metabolism in skeletal muscle. METHODS: Diabetic mice were randomly assigned to the diabetes group (T2DM, n=11) and the HIIT group (n=11), and age-matched wild type mice were assigned as the control group (CON, n=11). HIIT was performed on a motored mice treadmill at 15° inclination 5 days/week for 8 weeks. The mice were trained with a starting speed of 10m/min, where after HIIT consisted of 10 bouts of 4 min high-intensity treadmill running, interspersed by 2 min complete rest. The pace during HIIT was increased gradually from 16 to 26 m/min over eight weeks. The fasting blood glucose, glucose tolerance was measured one week before the end of the experiment, and the gastrocnemius muscles of mice were collected 36h after the last exercise. The fat content of skeletal muscle was detected by Oil Red O staining. Protein expression of ACC, HMGCR, Cpt-1α, and CD36 was measured with Western blot. RESULTS: The fasting blood glucose was decreased in the HIIT mice when compared to that in the T2DM mice (17.6±0.72 vs. 19.8±0.74 mmol/L, p<0.01). Glucose tolerance and the area under the curve (3325±126.4 vs. 3737±38. mmol/L·min, p<0.01) were improved after HIIT treatment when compared to that in the T2DM mice. Skeletal muscle exhibited a substantial amount of lipid deposition in the T2DM group, which was markedly alleviated in the HIIT group (p<0.05). In the skeletal muscle, HIIT treated mice showed significantly decreased protein expression related to lipogenesis, including reductions in ACC (0.39-fold, p<0.01) and HMGCR (0.52-fold, p<0.01). Expectedly, the protein expression level of Cpt-1α (1.6-fold, p<0.01) and CD36 (1.78-fold, p<0.01) was significantly enhanced by HIIT. CONCLUSION: HIIT improves insulin resistance was, at least partly, through deduces lipogenesis and increases lipolysis in skeletal muscle in the T2DM mice.

Antidiabetic and anti-inflammatory effects of two Fabaceae extracts against streptozotocin induced diabetic impairment in male rats

The present study aimed to investigate the antidiabetic and anti-inflammatory effects of Trifolium alexandrinum (TA) and Trifolium Pretense (TP) against streptozotocin induced diabetic impairment in male rats. Forty adult Wistar albino male rats were divided into four groups: Group 1, Control; Group 2, streptozotocin (STZ); Group 3, STZ + TA –treated group and Group 4, STZ + TP–treated group. TA and TP showed a significant reduction in the blood glucose, glycosylated hemoglobin (Hb A1C) levels and elevation in insulin and C-peptide. They restored the glycogen content of liver and skeletal muscle, also showed improvements in the activities of α-amylase, carbohydrate metabolic enzymes, lipase and lipid profile. Treatment with TA and TP extracts resulted in an improvement of the oxidative parameters and enhancement in the antioxidant enzymes in the pancreas and liver. While, pancreatic TNF-α, IL-1β, IL-6, NO, iNos and caspase-3 levels were significantly reduced with the treatment of TA and TP extracts. Administration of TA and TP extracts to diabetic rats revealed elevation in the GLUT4 levels of the skeletal muscle and pancreas. They caused up regulation in pancreatic GLUT2 gene expression. TA and TP extracts showed signs of regeneration of β-cells and improvement in the pancreatic tissue. It could be concluded that TA and TP extracts possess antioxidant and hypoglycemic potential resulting in reduction of the elevated oxidative stress and pro-inflammatory cytokines.

Mitochondrial Utilization of Competing Fuels Is Altered in Insulin Resistant Skeletal Muscle of Non-obese Rats (Goto-Kakizaki).

AimInsulin-resistant skeletal muscle is characterized by metabolic inflexibility with associated alterations in substrate selection, mediated by peroxisome-proliferator activated receptor δ (PPARδ). Although it is established that PPARδ contributes to the alteration of energy metabolism, it is not clear whether it plays a role in mitochondrial fuel competition. While nutrient overload may impair metabolic flexibility by fuel congestion within mitochondria, in absence of obesity defects at a mitochondrial level have not yet been excluded. We sought to determine whether reduced PPARδ content in insulin-resistant rat skeletal muscle of a non-obese rat model of T2DM (Goto-Kakizaki, GK) ameliorate the inhibitory effect of fatty acid (i.e., palmitoylcarnitine) on mitochondrial carbohydrate oxidization (i.e., pyruvate) in muscle fibers.MethodsBioenergetic function was characterized in oxidative soleus (S) and glycolytic white gastrocnemius (WG) muscles with measurement of respiration rates in permeabilized fibers in the presence of complex I, II, IV, and fatty acid substrates. Mitochondrial content was measured by citrate synthase (CS) and succinate dehydrogenase activity (SDH). Western blot was used to determine protein expression of PPARδ, PDK isoform 2 and 4.ResultsCS and SDH activity, key markers of mitochondrial content, were reduced by ∼10–30% in diabetic vs. control, and the effect was evident in both oxidative and glycolytic muscles. PPARδ (p < 0.01), PDK2 (p < 0.01), and PDK4 (p = 0.06) protein content was reduced in GK animals compared to Wistar rats (N = 6 per group). Ex vivo respiration rates in permeabilized muscle fibers determined in the presence of complex I, II, IV, and fatty acid substrates, suggested unaltered mitochondrial bioenergetic function in T2DM muscle. Respiration in the presence of pyruvate was higher compared to palmitoylcarnitine in both animal groups and fiber types. Moreover, respiration rates in the presence of both palmitoylcarnitine and pyruvate were reduced by 25 ± 6% (S), 37 ± 6% (WG) and 63 ± 6% (S), 57 ± 8% (WG) compared to pyruvate for both controls and GK, respectively. The inhibitory effect of palmitoylcarnitine on respiration was significantly greater in GK than controls (p < 10–3).ConclusionWith competing fuels, the presence of fatty acids diminishes mitochondria ability to utilize carbohydrate derived substrates in insulin-resistant muscle despite reduced PPARδ content.

Contribution of uremic dysbiosis to insulin resistance and sarcopenia.

Chronic kidney disease (CKD) leads to insulin resistance (IR) and sarcopenia, which are associated with a high mortality risk in CKD patients; however, their pathophysiologies remain unclear. Recently, alterations in gut microbiota have been reported to be associated with CKD. We aimed to determine whether uremic dysbiosis contributes to CKD-associated IR and sarcopenia. CKD was induced in specific pathogen-free mice via an adenine-containing diet; control animals were fed a normal diet. Fecal microbiota transplantation (FMT) was performed by oral gavage in healthy germ-free mice using cecal bacterial samples obtained from either control mice (control-FMT) or CKD mice (CKD-FMT). Vehicle mice were gavaged with sterile phosphate-buffered saline. Two weeks after inoculation, mice phenotypes, including IR and sarcopenia, were evaluated. IR and sarcopenia were evident in CKD mice compared with control mice. These features were reproduced in CKD-FMT mice compared with control-FMT and vehicle mice with attenuated insulin-induced signal transduction and mitochondrial dysfunction in skeletal muscles. Intestinal tight junction protein expression and adipocyte sizes were lower in CKD-FMT mice than in control-FMT mice. Furthermore, CKD-FMT mice showed systemic microinflammation, increased concentrations of serum uremic solutes, fecal bacterial fermentation products and elevated lipid content in skeletal muscle. The differences in gut microbiota between CKD and control mice were mostly consistent between CKD-FMT and control-FMT mice. Uremic dysbiosis induces IR and sarcopenia, leaky gut and lipodystrophy.

Transcriptome changes associated with fat deposition in the longissimus thoracis of Korean cattle following castration.

The castration of bulls increases the intramuscular fat (IMF) content in skeletal muscle. However, the biological processes of IMF accumulation in skeletal muscle after castration are not completely understood at the molecular level. This study examined the global transcriptomic changes in the longissimus thoracis muscle (LT) of bulls following castration using RNA sequencing (RNA-Seq) and identified new genes or pathways associated with beef quality. Ten bulls and 10 steers castrated at 6months of age were slaughtered at 26 and 32months of age respectively. For transcriptome analysis, six LT samples from three bulls and three steers were selected based on age, carcass weight, carcass quantity and beef quality grades. Using RNA-Seq, transcriptomic profiles of the LT were compared between bulls and steers. In all, 640 of the 18,027 genes identified through RNA-Seq were differentially expressed genes (DEGs) between bulls and steers. Pathway analysis of these 640 DEGs showed significant (p<.05) changes in seven Kyoto Encyclopedia of Genes and Genomes pathways, and the most significant terms were complement and coagulation cascade pathways. The transcriptomic expression patterns of 10 genes in the complement and coagulation cascades were validated using all animals through quantitative real-time polymerase chain reaction analysis. In conclusion, transcriptome changes associated with the complement and coagulation cascade pathways provide novel insights into understanding molecular mechanisms responsible for IMF accumulation following castration in beef cattle.

An improvement in skeletal muscle mitochondrial capacity with short‐term aerobic training is associated with changes in Tribbles 1 expression

Exercise training and physical activity are known to be associated with high mitochondrial content and oxidative capacity in skeletal muscle. Metabolic diseases including obesity and insulin resistance are associated with low mitochondrial capacity in skeletal muscle. Certain transcriptional factors such as PGC‐1α are known to mediate the exercise response; however, the precise molecular mechanisms involved in the adaptation to exercise are not completely understood. We performed multiple measurements of mitochondrial capacity both in vivo and ex vivo in lean or overweight individuals before and after an 18‐day aerobic exercise training regimen. These results were compared to lean, active individuals. Aerobic training in these individuals resulted in a marked increase in mitochondrial oxidative respiratory capacity without an appreciable increase in mitochondrial content. These adaptations were associated with robust transcriptome changes. This work also identifies the Tribbles pseudokinase 1, TRIB1, as a potential mediator of the exercise response in human skeletal muscle.

Effects of voluntary wheel running on mitochondrial content and dynamics in rat skeletal muscle.

This study reports that in rat skeletal muscle the proteins specifically responsible for mitochondrial dynamics, mitofusin-2 (MFN2) and mitochondrial dynamics protein 49 (MiD49), are higher (p < 0.05) in oxidative soleus (SOL) muscle compared with predominantly glycolytic extensor digitorum longus (EDL) muscle, but not seen for optic atrophy 1 (OPA1; p = 0.06). Markers of mitochondrial content, complex I component, NADH:Ubiquinone oxidoreductase subunit A9 (NDUFA9) and complex IV protein, cytochrome C oxidase subunit IV (COXIV; p < 0.05) were also higher in SOL compared with EDL muscle; however, there was no difference in mitochondrial content between muscles, as measured using a citrate synthase assay (p > 0.05). SOL and EDL muscles were compared between age-matched sedentary rats that were housed individually with (RUN) or without (SED) free-access to a running wheel for 12 weeks and showed no change in mitochondrial content, as examined by the abundances of NDUFA9 and COXIV proteins, as well as citrate synthase activity, in either muscle (p > 0.05). Compared to SED animals, MiD49 and OPA1 were not different in either EDL or SOL muscles, and MFN2 was higher in SOL muscles from RUN rats (p < 0.05). Overall, these findings reveal that voluntary wheel running is an insufficient stimulus to result in a significantly higher abundance of most markers of mitochondrial content or dynamics, and it is likely that a greater stimulus, such as either adding resistance to the wheel or an increase in running volume by using a treadmill, is required for mitochondrial adaptation in rat skeletal muscle.

Neck circumference is associated with adipose tissue content in thigh skeletal muscle in overweight and obese premenopausal women

Neck circumference (NC) has been proposed as a simple and practical tool, independently associated with cardiometabolic risk factors. However, the association of NC with inter-muscular adipose tissue (IMAT) is still to be determined. We aimed to examine the association of NC with thigh IMAT, and visceral adipose tissue (VAT) measured with computed tomography (CT) in overweight/obese women. 142 premenopausal overweight and obese Caucasian women participated in this cross-sectional study. NC was measured with an inextensible metallic tape above the thyroid cartilage according to International Society for Advancement of Kinanthropometry protocol. Thigh IMAT and VAT volumes were measured with a single cross-sectional CT. Regarding the covariates, fat mass (FM) was assessed with dual-energy x-ray absorptiometry and physical activity was objectively measured with accelerometry. NC was positively associated with thigh IMAT and VAT volumes (standardized β coefficient: β = 0.45, P-value = ≤0.001, β = 0.60, P = ≤ 0.001; respectively), which persisted after adjusting for age, height, overall FM or moderate-to-vigorous physical activity. Our findings show that NC is associated with thigh IMAT volume in overweight and obese premenopausal Caucasian women, regardless of the amount of lower-body fatness. These results suggest underscoring the relevance of NC as a marker of adipose tissue content in thigh skeletal muscle.

Contractility and Myofibrillar Content in Skeletal Muscle are Decreased During Post-Sepsis Recovery, But Not During the Acute Phase of Sepsis.

Convalescence in humans after severe sepsis occurs over weeks to months and is associated with prolonged functional disabilities and impaired quality-adjusted survival. While much is known regarding the acute early phase of sepsis, there is a knowledge gap pertaining to restoration of muscle mass and function after elimination of the septic nidus. We used a sepsis-recovery model-where cecal-ligation-puncture (CLP) was performed in adult male mice followed 24 h later by removal of the cecum and antibiotic treatment-to assess changes in the abundance of muscle contractile proteins and function during the acute phase of sepsis (24 h post-CLP) and during the recovery phase (day 10 post-CLP). Although body weight and food consumption decreased acutely with sepsis, both had normalized by day 10; however, extensor digitorum longus mass remained decreased 10%. During acute sepsis, there were few contractile defects or significant changes in contractile proteins. In contrast, during sepsis recovery, specific maximum isometric twitch and specific maximum tetanic force were decreased ≈50%, compared with time-matched pair-fed controls, and defects were independent of the concomitant reduction in muscle mass. Force generation in sepsis-recovery mice was decreased 30% with increasing stimulus frequency. Contractile defects during sepsis-recovery were associated with 50% to 90% reductions in thin filament (troponin T, troponin I, tropomyosin, α-sarcomeric actin), thick filament (myosin heavy and myosin light chains), Z-disc (α-actinin 3), and M-band (myomesin-2) proteins, but no change in the intermediate filaments desmin and vimentin. During sepsis recovery, myofibrillar protein synthesis did not differ from control, but synthesis of sarcoplasmic proteins was increased 60%. These data suggest intrinsic defects in muscle contractile function exist during the recovery phase of sepsis and may negatively impact convalescence.

Training with blood flow restriction increases femoral artery diameter and thigh oxygen delivery during knee-extensor exercise in recreationally trained men.

Endurance-type training with blood flow restriction (BFR) increases maximum oxygen uptake ( ) and exercise endurance of humans. However, the physiological mechanisms behind this phenomenon remain uncertain. In the present study, we show that BFR-interval training reduces the peripheral resistance to oxygen transport during dynamic, submaximal exercise in recreationally-trained men, mainly by increasing convective oxygen delivery to contracting muscles. Accordingly, BFR-training increased oxygen uptake by, and concomitantly reduced net lactate release from, the contracting muscles during relative-intensity-matched exercise, at the same time as invoking a similar increase in diffusional oxygen conductance compared to the training control. Only BFR-training increased resting femoral artery diameter, whereas increases in oxygen transport and uptake were dissociated from changes in the skeletal muscle content of mitochondrial electron-transport proteins. Thus, physically trained men benefit from BFR-interval training by increasing leg convective oxygen transport and reducing lactate release, thereby improving the potential for increasing the percentage of that can be sustained throughout exercise. In the present study, we investigated the effect of training with blood flow restriction (BFR) on thigh oxygen transport and uptake, and lactate release, during exercise. Ten recreationally-trained men (50±5mLkg-1 min-1 ) completed 6weeks of interval cycling with one leg under BFR (BFR-leg; pressure: ∼180mmHg) and the other leg without BFR (CON-leg). Before and after the training intervention (INT), thigh oxygen delivery, extraction, uptake, diffusion capacity and lactate release were determined during knee-extensor exercise at 25% incremental peak power output (iPPO) (Ex1), followed by exercise to exhaustion at 90% pre-training iPPO (Ex2), by measurement of femoral-artery blood flow and femoral-arterial and -venous blood sampling. A muscle biopsy was obtained from legs before and after INT to determine mitochondrial electron-transport protein content. Femoral-artery diameter was also measured. In the BFR-leg, after INT, oxygen delivery and uptake were higher, and net lactate release was lower, during Ex1 (vs. CON-leg; P<0.05), with an 11% larger increase in workload (vs. CON-leg; P<0.05). During Ex2, after INT, oxygen delivery was higher, and oxygen extraction was lower, in the BFR-leg compared to the CON-leg (P<0.05), resulting in an unaltered oxygen uptake (vs. CON-leg; P>0.05). In the CON-leg, at both intensities, oxygen delivery, extraction, uptake and lactate release remained unchanged (P>0.05). Resting femoral artery diameter increased with INT only in the BFR-leg (∼4%; P<0.05). Oxygen diffusion capacity was similarly raised in legs (P<0.05). Mitochondrial protein content remained unchanged in legs (P>0.05). Thus, BFR-interval training enhances oxygen utilization by, and lowers lactate release from, submaximally-exercising muscles of recreationally-trained men mainly by increasing leg convective oxygen transport.

Immobilization leads to alterations in intracellular phosphagen and creatine transporter content in human skeletal muscle.

The role of dysregulated intracellular creatine (Cr) metabolism in disuse atrophy is unknown. In this study, skeletal muscle biopsy samples were obtained after 7 days of unilateral leg immobilization (IMMOB) and from the nonimmobilized control limb (CTRL) of 15 healthy men (23.1 ± 3.5 yr). Samples were analyzed for fiber type cross-sectional area (CSA) and creatine transporter (CreaT) at the cell membrane periphery (MEM) or intracellular (INT) areas, via immunofluorescence microscopy. Creatine kinase (CK) and AMP-activated protein kinase (AMPK) were determined via immunoblot. Phosphocreatine (PCr), Cr, and ATP were measured via enzymatic analysis. Body composition and maximal isometric knee extensor strength were assessed before and after disuse. Leg strength and fat-free mass were reduced in IMMOB (~32% and 4%, respectively; P < 0.01 for both). Type II fiber CSA was smaller (~12%; P = 0.028) and intramuscular PCr lower (~13%; P = 0.015) in IMMOB vs. CTRL. CreaT protein was greater in type I fibers in both limbs (P < 0.01). CreaT was greater in IMMOB vs. CTRL (P < 0.01) and inversely associated with PCr concentration in both limbs (P < 0.05). MEM CreaT was greater than INT CreaT in type I and II fibers of both limbs (~14% for both; P < 0.01 for both). Type I fiber CreaT tended to be greater in IMMOB vs. CTRL (P = 0.074). CK was greater and phospho-to-total AMPKThr172 tended to be greater, in IMMOB vs. CTRL (P = 0.013 and 0.051, respectively). These findings suggest that modulation of intracellular Cr metabolism is an adaptive response to immobilization in young healthy skeletal muscle.

Effects of a Ketogenic Diet Containing Medium-Chain Triglycerides and Endurance Training on Metabolic Enzyme Adaptations in Rat Skeletal Muscle

Long-term intake of a ketogenic diet enhances utilization of ketone bodies, a particularly energy-efficient substrate, during exercise. However, physiological adaptation to an extremely low-carbohydrate diet has been shown to upregulate pyruvate dehydrogenase kinase 4 (PDK4, a negative regulator of glycolytic flux) content in skeletal muscle, resulting in impaired high-intensity exercise capacity. This study aimed to examine the effects of a long-term ketogenic diet containing medium-chain triglycerides (MCTs) on endurance training-induced adaptations in ketolytic and glycolytic enzymes of rat skeletal muscle. Male Sprague-Dawley rats were placed on either a standard diet (CON), a long-chain triglyceride-containing ketogenic diet (LKD), or an MCT-containing ketogenic diet (MKD). Half the rats in each group performed a 2-h swimming exercise, 5 days a week, for 8 weeks. Endurance training significantly increased 3-oxoacid CoA transferase (OXCT, a ketolytic enzyme) protein content in epitrochlearis muscle tissue, and MKD intake additively enhanced endurance training–induced increases in OXCT protein content. LKD consumption substantially increased muscle PDK4 protein level. However, such PDK4 increases were not observed in the MKD-fed rats. In conclusion, long-term intake of ketogenic diets containing MCTs may additively enhance endurance training–induced increases in ketolytic capacity in skeletal muscle without exerting inhibitory effects on carbohydrate metabolism.

Proteome alterations associated with the oleic acid and cis-9, trans-11 conjugated linoleic acid content in bovine skeletal muscle

Proteome alterations associated with the oleic acid and cis-9, trans-11 conjugated linoleic acid content in bovine skeletal muscle